Ixodes spp. tick-associated spirochetes were isolated during the preceding year from the blood, skin, and cerebrospinal fluid of Lyme disease patients. This finding together with demonstration of antibody responses by Lyme disease patients to several components of the spirochetes indicates that the tick-associated spirochetes are the etiological agents of Lyme disease. With biochemical and immunochemical techniques, we are identifying the major antigens of these spirochetes and studying the pathogenesis of Lyme disease.